Abstract:
AIMS:In Alzheimer's disease (AD), microglial activation prompted by the presence of amyloid has been proposed as an important contributor to the neurodegenerative process. Conversely following Aβ immunization, phagocytic microglia have been implicated in plaque removal, potentially a beneficial effect. We have investigated the effects of Aβ42 immunization on microglial activation and the relationship with Aβ42 load in human AD. METHODS:Immunostaining against Aβ42 and microglia (CD68 and HLA-DR) was performed in nine immunized AD cases (iAD - AN1792, Elan Pharmaceuticals) and eight unimmunized AD (cAD) cases. RESULTS:Although the Aβ42 load (% area stained of total area examined) was lower in the iAD than the cAD cases (P=0.036), the CD68 load was higher (P=0.046). In addition, in the iAD group, the CD68 level correlated with the Aβ42 load, consistent with the immunization upregulating microglial phagocytosis when plaques are present. However, in two long-surviving iAD patients in whom plaques had been extensively cleared, the CD68 load was less than in controls. HLA-DR quantification did not show significant difference implying that the microglial activation may have related specifically to their phagocytic function. CD68 and HLA-DR loads in the pons were similar in both groups, suggesting that the differences in microglial activation in the cortex were due to the presence of AD pathology. CONCLUSION:Our findings suggest that Aβ42 immunization modifies the function of microglia by increasing their phagocytic activity and when plaques have been cleared, the level of phagocytosis is decreased below that seen in unimmunized AD.
journal_name
Neuropathol Appl Neurobioljournal_title
Neuropathology and applied neurobiologyauthors
Zotova E,Holmes C,Johnston D,Neal JW,Nicoll JA,Boche Ddoi
10.1111/j.1365-2990.2010.01156.xsubject
Has Abstractpub_date
2011-08-01 00:00:00pages
513-24issue
5eissn
0305-1846issn
1365-2990journal_volume
37pub_type
杂志文章abstract:AIMS:The serotonin 2A receptor (HTR2A) is widely expressed in the brain and involved in the modulation of fear, mood, anxiety and other symptoms. HTR2A and HTR2A gene variations are implicated in depression, schizophrenia, anxiety and obsessive-compulsive disorder. To understand HTR2A signalling changes in psychiatric ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12167
更新日期:2015-06-01 00:00:00
abstract::Two HIV-positive male patients presented with a variety of symptoms including hemiparesis, unsteadiness, progressive loss of vision and poor memory. There were multiple non-enhancing lesions shown by CT scan in the white matter of the cerebral hemispheres. Specimens obtained by burr-hole biopsy showed the features of ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1989.tb01242.x
更新日期:1989-09-01 00:00:00
abstract::Mitochondrial abnormalities, in particular the accumulation of mitochondrial DNA mutations, have been proposed as a potential cause of normal ageing. One group of patients with mtDNA disorders have a nuclear DNA defect which accelerates the chronological accumulation of mitochondrial DNA mutations. These patients prov...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2001.00315.x
更新日期:2001-06-01 00:00:00
abstract::A disorder of the gracile axonal dystrophy (GAD) mutant mouse is characterized by a neuromuscular disease with sensory ataxia (detectable 30 days after birth) and paresis of the hindlimbs (detectable at 80 days). In the sensory ataxia stage, histological study of the primary sensory system shows that, in addition to t...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1992.tb00789.x
更新日期:1992-06-01 00:00:00
abstract:INTRODUCTION:Cerebral ischaemia is the defining pathophysiological abnormality in most forms of vascular dementia (VAD), but the pathogenesis of the dementia remains poorly understood. In Alzheimer's disease (AD), there is early loss of synaptic proteins, but these have been little studied in VAD. MATERIALS AND METHOD...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12215
更新日期:2015-06-01 00:00:00
abstract::Inflammatory cells from the meninges of guinea-pigs with acute EAE have been isolated and quantitated. A mean of 7.5 x 10(6) cells were recovered from the brains of animals showing clinical signs of disease in contrast to only 1.5 x 10(6) cells in the controls. The immunological specificity of the meningeal inflammato...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1981.tb00082.x
更新日期:1981-03-01 00:00:00
abstract::A case of congenital amaurotic idiocy, a subgroup of the neurovisceral lipidoses, is described. This is a rare condition of which only five cases have been reported previously. The brain was small and firm with marked neuronal loss and gliosis. Granular material with histochemical properties of the ceroid-lipofuscin g...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1985.tb00041.x
更新日期:1985-11-01 00:00:00
abstract::Semliki Forest virus infections in mice produce an encephalitis with demyelination. If before giving the virus the mice are treated with muramyl dipeptide in Freund's incomplete adjuvant, there is a significant increase in demyelination. If ovalbumin is added to the above and then followed after an interval by a secon...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1988.tb01339.x
更新日期:1988-11-01 00:00:00
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journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12182
更新日期:2015-06-01 00:00:00
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journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,meta分析
doi:10.1111/nan.12430
更新日期:2018-04-01 00:00:00
abstract::Human tumour xenografts maintained in nude mice are a valuable research tool. The passaging and maintenance of human tumour xenografts in immune-deficient animals are expensive and labour-intensive. This study presents a protocol that permits long-term cryopreservation of viable glioblastoma xenograft tissue pieces in...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2000.026002172.x
更新日期:2000-04-01 00:00:00
abstract::Alzheimer's and Parkinson's diseases (AD, PD) are among the most common neurodegenerative disorders in adults. Both AD and PD have a complex aetiology, and it is widely considered that genetic factors, acting independently or in concert with other genetic and/or environmental factors, modify the risk of developing the...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::We have examined the influence that axons may have on the expression of proteolipid protein (PLP), the major myelin protein of the CNS. Partial transections were made of the optic nerve of adult rats to produce approximately a 50% loss of axons. Twenty-eight days after lesioning, sections of the distal nerves were imm...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1991.tb00725.x
更新日期:1991-08-01 00:00:00
abstract:AIMS:To explore alterations in the expression of genes encoding enzymes involved in purine metabolism in Parkinson's disease (PD) brains as purines are the core of the DNA, RNA, nucleosides and nucleotides which participate in a wide variety of crucial metabolic pathways. METHODS:Analysis of mRNA using real-time quant...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12221
更新日期:2015-12-01 00:00:00
abstract::Cerebrospinal fluid (CSF) was taken from strain 13 guinea pigs in various stages of chronic relapsing experimental allergic encephalomyelitis, the spinal cords removed for histological examination and meningeal stretch preparations made. CSF cells were counted and characterized by morphological studies, anti-IgG and a...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1983.tb00111.x
更新日期:1983-05-01 00:00:00
abstract::Scrapie is a prion disease or transmissible spongiform encephalopathy (TSE) of sheep, goats and moufflon. As with its human counterparts, pathology consists of vacuolation, gliosis and accumulations of abnormal forms of a host prion protein (PrPd) in the brain of affected individuals. Immunohistochemical methods can b...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2007.00868.x
更新日期:2007-08-01 00:00:00
abstract:AIMS:Amyloid-β (Aβ) oligomers trigger synaptic degeneration that precedes plaque and tangle pathology. However, the signalling molecules that link Aβ oligomers to synaptic pathology remain unclear. Here, we addressed the potential role of RAPGEF2 as a novel signalling molecule in Aβ oligomer-induced synaptic and cognit...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12686
更新日期:2020-12-20 00:00:00
abstract::The cellular distribution of the lysosomal proteinase cathepsin D was studied in a series of 76 neoplasms and 18 non-neoplastic tissues from the human central nervous system, using a well-characterized polyclonal antibody in a peroxidase-antiperoxidase technique. In the normal and developing brain, cathepsin D is conf...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1990.tb00930.x
更新日期:1990-02-01 00:00:00
abstract::A few nanograms of tetanus toxin injected into a rat hippocampus causes a chronic epileptic syndrome characterized by brief seizures that recur intermittently for about 6 weeks. Cognitive and other behavioural impairments persist after the seizures and other epileptic electrographic activity have remitted, and may be ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1992.tb00764.x
更新日期:1992-02-01 00:00:00
abstract:AIMS:Secreted protein, acidic and rich in cysteine (SPARC) is a regulator of cell-matrix interaction and has been associated with tumour stage and patient survival in various malignancies. As no large-scale study has yet been undertaken, we investigated human brain and astrocytomas for SPARC expression and associations...
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doi:10.1111/j.1365-2990.2010.01072.x
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abstract::Dementia with Lewy bodies (DLB) is characterized by the widespread presence of Lewy bodies (LBs) in the brain. alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain. We compared alpha-synuclein 112 and alpha-syn...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2004.00572.x
更新日期:2004-12-01 00:00:00
abstract:AIMS:Increasing evidences suggest a similarity in the pathophysiological mechanisms of neuronal cell death in amyotrophic lateral sclerosis (ALS) and myofibre degeneration in sporadic inclusion body myositis (sIBM). The aim of this study is to elucidate the involvement of ALS-causing proteins in the pathophysiological ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2012.01297.x
更新日期:2013-06-01 00:00:00
abstract::Ultrastructural studies of spongiform encephalopathy (SE) reveal no very early pathological changes in kuru where membrane lamellation has been reported. This observation is challenged. In the later stages of SE, two main theories are examined--the spiroplasma theory and the prion (6 nm filament) theory. Neither are s...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1986.tb00047.x
更新日期:1986-03-01 00:00:00
abstract::In a previous study, we described the inhibitory effects of the growth factor-antagonist, trapidil, on spontaneously occurring oligodendrocyte remyelination in the rat spinal cord following lysolecithin-induced demyelination [30]. The objective of the present study was to further investigate the mechanisms of trapidil...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.1998.00148.x
更新日期:1998-12-01 00:00:00
abstract::Oestrogen receptors and progesterone receptors were measured by an isoelectric focussing technique in cytosols from cryostat sections of eight human pituitary adenomas. Cryostat sections adjacent to the assayed sample were stained for anterior pituitary hormones using the peroxidase-antiperoxidase technique, and the c...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1986.tb00158.x
更新日期:1986-11-01 00:00:00
abstract::Transferase dUTP nick-end labelling (TUNEL) analysis was used to compare the occurrence of cell death in the cerebral wall of cocaine-exposed and drug-naïve monkey fetuses. The rhesus monkeys providing the drug-exposed fetuses received 10 mg/kg of cocaine orally (in fruit treats) in the morning and in the evening betw...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.1999.00211.x
更新日期:1999-12-01 00:00:00
abstract::Axonal damage in multiple sclerosis (MS) is correlated to disease progression. Early axonal damage may be compensated for by regenerative processes. Growth-associated protein 43 (GAP-43) is a marker for axonal growth and synaptogenesis in various neurodegenerative diseases. We investigated the expression of GAP-43 in ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2006.00730.x
更新日期:2006-06-01 00:00:00
abstract::The brain is vulnerable to a number of acute insults, with traumatic brain injury being among the commonest. Neuroinflammation is a common response to acute injury and microglial activation is a key component of the inflammatory response. In the acute and subacute phase it is likely that this response is protective an...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/nan.12006
更新日期:2013-02-01 00:00:00
abstract::The spectrum of glioneuronal lesions underlying intractable epilepsies includes malformative pathologies like focal cortical dysplasia (FCD); and neoplastic lesions like gangliogliomas (GG) and dysembryoplastic neuroepithelial tumours (DNT). These may occur either singly or as dual lesions, having simultaneous presenc...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2006.00734.x
更新日期:2006-10-01 00:00:00
abstract:AIMS:Transition metals, oxidative stress and neuroinflammation have been proposed as part of a vicious cycle in central nervous system neurodegeneration. Our aim was to study the anti-inflammatory effect of pioglitazone, a peroxisome proliferative activated receptor-γ agonist, on iron-induced oxidative injury in rat br...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2010.01107.x
更新日期:2010-12-01 00:00:00